Effects of sleep restriction on adiponectin levels in healthy men and women

Objective

Population studies have consistently found that shorter sleep durations are associated with obesity and cardiovascular disease, particularly among women. Adiponectin is an adipocyte-derived, anti-inflammatory hormone that is related to cardiovascular disease risk. We hypothesized that sleep restriction would reduce adiponectin levels in healthy young adults.

Methods

74 healthy adults (57% men, 63% African American, mean age 29.9 years) completed 2 nights of baseline sleep at 10 h time in bed (TIB) per night followed by 5 nights of sleep restricted to 4 h TIB per night. An additional 8 participants were randomized to a control group that received 10 h TIB per night throughout the study. Plasma adiponectin levels were measured following the second night of baseline sleep and the fifth night of sleep restriction or control sleep.

Results

Sleep restriction resulted in a decrease in plasma adiponectin levels among Caucasian women (Z = −2.19, p = 0.028), but an increase among African American women (Z = −2.73, p = 0.006). No significant effects of sleep restriction on adiponectin levels were found among men. A 2 × 2 between-group analysis of covariance on adiponectin change scores controlling for BMI confirmed significant interactions between sleep restriction and race/ethnicity [F(1,66) = 13.73, p < 0.001], as well as among sleep restriction, race/ethnicity and sex [F(1,66) = 4.27, p = 0.043)].

Conclusions

Inflammatory responses to sleep loss appear to be moderated by sex and race/ethnicity; observed decreases in adiponectin following sleep restriction may be one avenue by which reduced sleep duration promotes cardiovascular risk in Caucasian women.     

The spinal precerebellar nuclei: calcium binding proteins and gene expression profile in the mouse

Sleep restriction is a widespread phenomenon, specifically in adolescents. This study investigated the impact of increasing sleep restriction in adolescents on cortisol levels and daytime sleepiness. Eighty-eight healthy adolescents were randomized to five sleep restriction protocols (four consecutive nights with 9, 8, 7, 6, or 5 h time in bed). Polysomnography (baseline and last experimental night) and multiple sleep latency test (day 6) data were obtained. Saliva cortisol levels were assessed half-hourly in the evening before and in the morning after the baseline and the last experimental night. Four nights of sleep restriction in healthy adolescents lead to a linear increase of objective sleepiness, but had no significant effect on evening or morning cortisol levels. The lack of detrimental effects of sleep restriction on cortisol levels might be due to compensation mechanisms during sleep.     

Anticipated next‐day demand affects the magnitude of the cortisol awakening response,but not subjective or objective sleep

Whilst the association between sleep and stress is well established, few studies have examined the effects of an anticipated stressor upon sleep and relevant physiological markers. The aim of the present study was to examine whether an anticipated stressor in the form of next‐day demand affects subjective and objective sleep, and multiple indices of the cortisol awakening response. Subjective and objective sleep and the cortisol awakening response were measured over three consecutive nights in 40 healthy adults in a sleep laboratory. During their second night, participants were informed that they would either be required to complete a series of demanding cognitive tasks, in a competition format, during the next day (anticipation condition; n = 22), or were given no instruction (sedentary condition; n = 18). Sleep was measured subjectively using sleep diaries, objectively using polysomnography, and saliva was measured at awakening, +15, +30, +45 and +60 min each morning, from which cortisol awakening response measurement indices were derived: awakening cortisol levels, the mean increase in cortisol levels and total cortisol secretion. There were no between‐group differences in subjective or objective sleep in the night preceding the anticipated demand; however, compared with the sedentary condition, those in the anticipation group displayed a larger mean increase in cortisol levels, representing the cortisol awakening response magnitude, on the morning of the anticipated demand. Overall, the results suggest that whilst anticipated stress affected the subsequent cortisol awakening response, subjective and objective sleep remained undisturbed. It is possible that the timing of an anticipated stressor, rather than its expected duration, may influence subsequent sleep disruption.     

A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normal-weight healthy men

Sleep loss is currently proposed to disturb endocrine regulation of energy homeostasis leading to weight gain and obesity. Supporting this view, a reduction of sleep duration to 4 h for two consecutive nights has recently been shown to decrease circulating leptin levels and to increase ghrelin levels, as well as self-reported hunger. We hypothesized that similar endocrine alterations occur even after a single night of sleep restriction. In a balanced order, nine healthy normal-weight men spent three nights in our sleep laboratory separated by at least 2 weeks: one night with a total sleep time of 7 h, one night with a total sleep time of 4.5 h and one night with total sleep deprivation (SD). On a standard symptom-rating scale, subjects rated markedly stronger feelings of hunger after total SD than after 7 h sleep (3.9 ± 0.7 versus 1.7 ± 0.3; P  = 0.020) or 4.5 h sleep (2.2 ± 0.5; P  = 0.041). Plasma ghrelin levels were 22 ± 10% higher after total SD than after 7 h sleep (0.85 ± 0.06 versus 0.72 ± 0.04 ng mL⁻¹; P  = 0.048) with intermediate levels of the hormone after 4.5 h sleep (0.77 ± 0.04 ng mL⁻¹). Serum leptin levels did not differ between conditions. Feelings of hunger as well as plasma ghrelin levels are already elevated after one night of SD, whereas morning serum leptin concentrations remain unaffected. Thus, our results provide further evidence for a disturbing influence of sleep loss on endocrine regulation of energy homeostasis, which on the long run may result in weight gain and obesity.     

Sleep disturbances and depressed mood: a harmful combination associated with increased leptin levels in women with normal weight

Leptin, involved in energy regulation and contributor to cardiovascular disease, has been implicated to play a role in depression and sleep disturbances, two closely intertwined conditions. Previous results investigating leptin level alterations either in sleep disorders or in depression have been inconsistent.We investigate the association between leptin levels and the different combinations of depressed mood and sleep disturbances in 1369 subjects (706 men, 663 women), derived from the population-based MONIKA/KORA study. As leptin regulation is known to differ by sex and weight, analyses were performed in normal weight and overweight men and women separately. We found a highly significant association between leptin levels and the combination of depressed mood and sleep disturbances in normal-weight women (BMI ≤ 25) (p < 0.01). No associations were found in men and in overweight women. Our results suggest that leptin regulation in depressed mood and sleep disturbances very much depend on sex and weight.     

Cyclic alternating pattern and sleep quality in healthy subjects—Is there a first-night effect on different approaches of sleep quality?

Objective

Cyclic alternating pattern (CAP) is defined as periodic EEG activity during NREM sleep that reflects unstable sleep and represents a marker of instability of the sleep process. The aim of the present investigation was to analyze sleep quality of 28 healthy subjects (mean age 53.3 ± 21.3 years) over two consecutive nights and determine potential differences between them (“first-night effect”).

Methods

Evaluations comprised objective and subjective sleep variables as well as macrostructural and microstructural variables of sleep.

Results

Macrostructural analysis showed significant differences between the first and the second sleep laboratory night in REM latency (122.39 ± 60.46 min vs. 95.43 ± 36.60 min; T = 3.431; p = 0.002) and the amount of sleep stage 1 (42.60 ± 21.80 min vs. 39.70 ± 18.95 min; T = 2.223; p = 0.035). Microstructural analysis revealed a significant decrease in the CAP rate (1st night: 33.29%; 2nd night: 26.34%; T = 3.288; p = 0.003) and in the amount of subtype A2 (74.79 ± 43.47 vs. 58.50 ± 23.22; T = 2.185; p = 0.038). Subjective variables also demonstrated a significant increase of drive (T = 2.564; p = 0.016).

Conclusion

Healthy subjects show hardly any macrostructural differences between the first and the second night in the sleep laboratory. On the microstructural level differences in CAP variables were found.

Significance

Microstructural analysis can be seen as a further approach to the classification of sleep and CAP turned out to be sensitive to environmental influences on sleep.     

Self-reported menopausal symptoms in a racially diverse population and soy food consumption

Objectives

Evaluate the association of self-reported vasomotor symptom (VMS) frequency with race/ethnicity among a diverse midlife US population and explore menopause symptom differences by dietary soy isoflavone (genistein + daidzein) consumption.

Study design

Cross-sectional population-based study of peri- and postmenopausal women, ages 45–58.

Outcomes

Recent VMS frequency, VMS ever; recent symptom bother (hot flashes, night sweats, headache and joint-ache).

Results

Of 18,500 potentially eligible women, 9325 returned questionnaires (50.4% response); 3691 were excluded (premenopausal, missing data, taking hormones). Of 5634 remaining women, 82.1% reported hot flashes ever, 73.1% reported night sweats ever; 48.8% and 38.6% reported recent hot flashes or night sweats, respectively. Compared with White women, Chinese, Japanese, Vietnamese, other Asian (each p < 0.001) and Filipino (p < 0.01) women less commonly reported ever having hot flashes; Asian women less commonly reported recent VMS bother (p < 0.001). Black women more commonly reported hot flashes ever (p < 0.05) and recent VMS bother (p < 0.05). Compared with non-Hispanic White women, Hispanic women were less likely to report hot flashes (p < 0.05) or night sweats (p < 0.001) ever. Women were classified by isoflavone consumption: (1) none (n = 1819), (2) 0.01–4.30 mg/day (n = 1931), (3) 4.31–24.99 mg/day (n = 1347) and (4) ≥25 mg/day (n = 537). There were no group differences in recent VMS number/day: (1) 7.0 (95% CI 6.5, 7.5); (2) 6.4 (95% CI 6.0, 7.1); (3) 7.0 (95% CI 6.3, 8.2); and (4) 6.8 (95% CI 6.1, 7.7).

Conclusions

Menopausal symptoms, independent of isoflavone intake, varied considerably by race/ethnicity and were least common among Asian races.     

Sympathetic overactivity and plasma leptin levels in Rett syndrome

Rett syndrome (RTT) is a severe developmental–neurological disorder, characterized by profound and progressive loss of intellectual functioning, occurring after a period (of at least 6 months) of normal development with classic stereotype hand movements, gait ataxia, jerky truncal ataxia, deceleration of brain and body organ growth and cardiac dysautonomia. Pathogenesis of sympathetic overactivity in RTT is unknown, but a previous study observed increased plasma leptin levels in Rett girls and it is well known the role of leptin in the regulation of sympathetic nervous system activity. Aim of our study is to evaluate a relationship between plasma leptin levels and sympathetic activity in RTT. Thirty-two female patients (12.1 ± 6.3 years), affected by RTT were enrolled in the study. In all the subjects, we analyzed heart rate variability, QT corrected interval and plasma leptin levels. A significant correlation was found between plasma leptin levels and LF/HF (expression of sympatho-vagal balance) (Spearman r = 0.44, p = 0.001). There is also a significant negative correlation between HF component (expression of vagal activity) and plasma leptin levels (Spearman r = −0.037, p = 0.03) and a positive correlation between LF component and plasma leptin levels (Spearman r = 0.047, p = 0.01). These results show that in RTT higher plasma leptin levels appear to be associated with sympathetic overactivity, suggesting a role for leptin in cardiac dysautonomia.     

Women with PTSD have lower basal salivary cortisol levels later in the day than do men with PTSD: A preliminary study

Acute stress responses of women are typically more reactive than that of men. Women, compared to men, may be more vulnerable to posttraumatic stress disorder (PTSD). Whether there are differences between women and men with PTSD in levels of the stress hormone, cortisol, was investigated in a pilot study. Methods: women (n = 6) and men (n = 3) motor vehicle accident (MVA) survivors, with PTSD, had saliva collected at 1400 h, 1800 h, and 2200 h. Cortisol levels in saliva were measured by radioimmunoassay. An interaction between gender and time of sample collection was observed due to women's cortisol levels being lower and decreasing over time, whereas men's levels were higher and increased across time of day of collection. Results of this pilot study suggest a difference in the pattern of disruption of glucocorticoid secretion among women and men with PTSD. Women had greater suppression of their basal cortisol levels than did men; however, the diurnal pattern for cortisol levels to decline throughout the day was observed among the women but not the men.     

Use of hair cortisol analysis to detect hypercortisolism during active drinking phases in alcohol-dependent individuals

The assessment of cortisol levels in human hair has recently been suggested to provide a retrospective index of cumulative cortisol exposure over periods of up to 6 months. The current study examined the utility of hair cortisol analysis to retrospectively detect hypercortisolism during active drinking phases in alcoholics in acute withdrawal (n = 23), the normalisation of cortisol output in abstinent alcoholics (n = 25) and cortisol levels in age- and gender-matched controls (n = 20). Scalp-near 3-cm hair segments were sampled and analysed for cortisol content. Results showed three to fourfold higher cortisol levels in hair samples of alcoholics in acute withdrawal than in those of abstinent alcoholics (p < .001) or controls (p < .001), with no differences between the latter two groups. The current hair cortisol findings closely mirror results of previous research using well-established measures of systemic cortisol secretion and thus provide further validation of this novel method.     

Oral sensory and cephalic hormonal responses to fat and non-fat liquids in bulimia nervosa

Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics typically limit their food choices to low-fat “safe foods” and intermittently lose control and binge on high-fat “risk foods”. The aim of this study was to determine whether the oral sensory effects of a fat versus a non-fat milk product (i.e., traditional versus non-fat half-and-half) resulted in different subjective and hormonal responses in bulimic women (n = 10) compared with healthy women (n = 11). Naltrexone (50 mg PO) or placebo was administered 1 h before, and blood sampling began 30 min prior to and 29 min after, a 3 min portion controlled modified sham-feeding trial. Following an overnight fast, three morning trials (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a random double-blind fashion separated by at least 3 days. Overall, there were no differences between Fat and Non-Fat trials. Hunger ratings (p < 0.001) and pancreatic polypeptide levels (p < 0.05) were higher for bulimics at baseline. Bulimics also had overall higher ratings for nausea (p < 0.05), fatty taste (p < 0.01), and fear of swallowing (p < 0.005). Bulimics had ∼ 40% higher total ghrelin levels at all time points (p < 0.001). Hormones and glucose levels were not altered by the modified sham-feeding paradigm. Naltrexone, however, resulted in an overall increase in blood glucose and decrease in ghrelin levels in both groups (p < 0.05, for both). These data suggest that bulimic women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.     

Leptin and hunger levels in young healthy adults after one night of sleep loss

Short‐term sleep curtailment associated with activation of the stress system in healthy, young adults has been shown to be associated with decreased leptin levels, impaired insulin sensitivity, and increased hunger and appetite. To assess the effects of one night of sleep loss in a less stressful environment on hunger, leptin, adiponectin, cortisol and blood pressure/heart rate, and whether a 2‐h mid‐afternoon nap reverses the changes associated with sleep loss, 21 young healthy individuals (10 men, 11 women) participated in a 7‐day sleep deprivation experiment (four consecutive nights followed by one night of sleep loss and two recovery nights). Half of the subjects were randomly assigned to take a mid‐afternoon nap (14:00–16:00 hours) the day following the night of total sleep loss. Serial 24‐h blood sampling and hunger scales were completed on the fourth (predeprivation) and sixth day (postdeprivation). Leptin levels were significantly increased after one night of total sleep loss, whereas adiponectin, cortisol levels, blood pressure/heart rate, and hunger were not affected. Daytime napping did not influence the effects of sleep loss on leptin, adiponectin, or hunger. Acute sleep loss, in a less stressful environment, influences leptin levels in an opposite manner from that of short‐term sleep curtailment associated with activation of the stress system. It appears that sleep loss associated with activation of the stress system but not sleep loss per se may lead to increased hunger and appetite and hormonal changes, which ultimately may lead to increased consumption of ‘comfort’ food and obesity.     

Factors related to increased daytime sleepiness during the menopausal transition as evaluated by the Epworth Sleepiness Scale

Background

Sleep disorders and sleep-apnea/hypopnea syndromes are very frequent in women, being misdiagnosed in many cases. The menopause, regardless of age, is associated to poor sleep quality and daytime sleepiness that can lead to impaired quality of life, and reduced productivity and functioning.

Objective

To assess daytime sleepiness and related risk factors among middle aged Ecuadorian women using the Epworth Sleepiness Scale (ESS).

Methods

In this cross-sectional study 149 women aged 40–59 years were assessed for hot flush presence and intensity using the Menopause Rating Scale (MRS) and requested to fill out the ESS and a questionnaire containing personal and partner data.

Results

Mean age of surveyed women was 47.6 ± 5.5 years, with 67.8% having less than 12 years of schooling, 33.6% being postmenopausal, and 2.7% on hormone therapy. A 10.1% were current smokers and 20.8% were sedentary. According to the MRS (item 1) 51.7% presented hot flushes, which were graded as severe–very severe in 42.8% of cases. Regarding the partner (n = 132), erectile dysfunction was present in 10.6%, premature ejaculation 6.1% and 17.4% abused alcohol. Mean total ESS score was 8 ± 4.4 (median 8), with 33.6% considered having some degree of daytime sleepiness (ESS score ≥10). Logistic regression analysis determined that postmenopausal status (OR 6.58, CI 95% [2.51–17.23], p = 0.001), sedentarism (OR 3.43, CI 95% [1.14–10.26], p = 0.02) and hot flush presence (OR 2.61, CI 95% [1.02–6.65], p = 0.04) among women were risk factors for increased daytime sleepiness (ESS total score ≥10) whereas partner faithfulness decreased this risk (OR 0.47, CI 95% [0.24–0.90], p = 0.02).

Conclusion

Increased daytime sleepiness in this middle aged series was related to female (hormonal status and sedentarism) and partner factors; several which are susceptible of intervention.     

The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of acute nighttime sleep restriction, wake time, and daytime napping

The cortisol awakening response (CAR) is presumed critically important for healthy adaptation. The current literature, however, is hampered by systematic measurement difficulties relative to awakening, especially with young children. While reports suggest the CAR is smaller in children than adults, well‐controlled research in early childhood is scarce. We examined whether robust CARs exist in 2‐ to 4‐year‐old children and if sleep restriction, wake timing, and napping influence the CAR (n = 7). During a 25‐day in‐home protocol, researchers collected four salivary cortisol samples (0, 15, 30, 45 min post‐wake) following five polysomnographic sleep recordings on nonconsecutive days after 4 hr (morning nap), 7 hr (afternoon nap), 10 hr (evening nap), 13 hr (baseline night), and 16 hr (sleep restriction night) of wakefulness (20 samples/child). The CAR was robust after nighttime sleep, diminished after sleep restriction, and smaller but distinct after morning and afternoon (not evening) naps. Cortisol remained elevated 45 min after morning and afternoon naps. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:412–422, 2012.     

Effects of postnatal environmental tobacco smoke on non-nutritive swallowing-breathing coordination in newborn lambs

While prenatal environmental tobacco smoke (ETS) exposure is a well-known risk factor for sudden infant death syndrome, the effect of postnatal ETS exposure is less clear. The objective of this study was to investigate the effect of postnatal ETS exposure on non-nutritive swallowing (NNS) and NNS-breathing coordination, which are crucial to prevent aspiration related-cardiorespiratory events. Eighteen newborn lambs (6 per group) were randomly exposed to either 10 cigarettes/day, 20 cigarettes/day or room air for 15 days. Lambs were instrumented for recording states of alertness, swallowing, electrocardiogram and breathing; recordings were performed in non-sedated lambs at the end of ETS exposure. Urinary cotinine/creatinine ratio confirmed relevant real-life exposure. Postnatal ETS exposure had no effect on NNS frequency but tended to decrease inspiratory NNS (p = 0.07) during quiet sleep. No effect on respiratory or heart rate (p > 0.6), apnea index (p = 0.2) or sleep states (p = 0.3) was observed. In conclusion, postnatal ETS exposure in lambs had only mild effects on NNS-breathing coordination.     

Labisia pumila extract regulates body weight and adipokines in ovariectomized rats

Objective

We investigated the effects of a standardized water extract of Labisia pumila var. alata (LPva), and compared to estrogen replacement (ERT), on body weight gain, uterus weight, adipose tissue mRNA and protein levels of adipokines in ovariectomized (OVX) rats.

Methods

Eight-week-old OVX Sprague-Dawley rats were administered orally with either 10 mg/kg/day (LPva10), 20 mg/kg/day (LPva20) or 50 mg/kg/day (LPva50) of LPva for 30 days. Sham-operated (Sham) and estrogen-treated OVX rats (ERT, 0.625 mg/kg/day) served as controls. Plasma adipokines were measured, and mRNA expressions of the adipokines were determined in the adipose tissues.

Results

ERT- and LPva50-treated OVX rats showed significantly less (p < 0.05) weight gain compared to untreated OVX rats. Ovariectomy caused plasma leptin levels to decrease significantly (p < 0.05), but when treated with LPva or ERT, plasma leptin increased significantly to levels higher or comparable to that seen in the Sham group. The mRNA expression of leptin was higher in the LPva-treated animals than in all other groups. In contrast, the elevated plasma resistin concentrations in OVX rats were significantly reduced in rats given ERT (p < 0.05) and LPva extracts (p < 0.05). There was no difference in adiponectin levels in all groups. The uterus to body weight ratio of untreated OVX rats was significantly low compared to Sham (p < 0.05), but showed dose-dependent increase upon treatment with LPva.

Conclusion

The present study provides first evidence that LPva exerts uterotrophic effect and regulates body weight gain by modulating secretion of leptin and resistin, and expression of the adipokines in adipose tissues.     

Do different delivery systems of hormone therapy have different effects on psychological symptoms in surgically menopausal women? A randomized controlled trial

Objective

To compare the influence of different delivery forms of estrogen therapy on menopausal and psychological symptoms in surgically menopausal women.

Study design

Surgically menopausal women were assigned to a 1-year-therapy with oral conjugated estrogen 0.625 mg/day (n = 35), intranasal 300 μg/day estradiol hemihidrate (n = 33), percutaneous gel 1.5 mg/day estradiol hemihidrate (n = 32) or no treatment (control group, n = 32). Serum E₂ and FSH levels, Kupperman's Scale used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year-therapy.

Results

After 1 year, the greatest increase in E₂ was in the oral group, followed by the transdermal gel, and then the intranasal group (oral vs transdermal gel: p = 0.022: oral vs intranasal: p = 0.0001; transdermal gel vs intranasal: p = 0.0001). All treatment groups improved significantly in total Kupperman index score and HARS (p < 0.05) with no difference between the groups. With regard to HDRS, all treatment groups improved significantly (p < 0.05) with the greatest improvement in the oral group, and no difference between transdermal gel and intranasal groups (oral vs transdermal gel: p = 0.015; oral vs intranasal: p = 0.001; transdermal gel vs intranasal: p = 0.735). Control group scored worse in all tests after study (p < 0.05). All scores correlated significantly with post-treatment serum E₂ and FSH levels (p < 0.001).

Conclusion

Oral, intranasal and percutaneous gel estradiol therapies significantly improve menopausal and psychological symptoms in surgically menopausal women with oral route better than transdermal gel and intranasal modalities against depressive mood.     

Hormonal and psycho-relational aspects of sexual function during menopausal transition and at early menopause

Objective

The aim of the present observational, cross-sectional study was to examine the effects of hormonal and psycho-relational variables on sexual function during menopausal transition and at early postmenopause in women with hot flushes.

Study design

The sample comprised 138 women referred to a clinic for the treatment of hot flushes. They were categorised according to their stage of menopausal transition using the STRAW criteria: early menopausal transition (EMT) if their menstrual cycle was 7 or more days different from normal; late perimenopause (LMT) if they had experienced 60 days or more of amenorrhoea; and early postmenopause (EPM) if their amenorrhoea had lasted for at least 12 months but less than 4 years.

Main outcome measures

Sexual function was measured by using the Female Sexual Function Index (FSFI), while anxiety (state and trait), depression, eating disorder and marital adjustment were evaluated by validated self-report questionnaires. Levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and estradiol (E2) were also measured.

Results

Overall sexual function varied significantly with stage of menopause, with total FSFI score less in EPM than in EMT (p = .009). A similar pattern was evident on FSFI sub-scales for sexual desire (p = .02), arousal (p = .01) orgasm (p = .01) and also pain (p = .02), but not for lubrication and satisfaction. Ratings for anxiety, depression and eating disorder did not differ across the menopausal sub-groups, and neither did ratings of marital adjustment. Both FT (p = .01) and DHEAS (p = .03) levels were slightly reduced at EPM in comparison with EMT, as were E2 levels (p = .001 EMT versus LMT; p = .0001 LMT versus EPM). In multiple regression analyses, plasma FT level was the only factor to predict FSFI full score (β = .48; p = 0.004) in women at EMT, while in women at LMT the depression score was the only factor to do so (β = −.62; p = 0.0001). The best model predicting FSFI full score at EPM included levels of DHEAS and E2 levels and state anxiety score.

Conclusions

Hormonal and some psychological variables are relevant to sexual function in symptomatic women during menopausal transition and at early menopause but their role differs with the specific stage of reproductive ageing.     

Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women

Serotonin modulates the activity of the hypothalamic–pituitary–adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT_1A). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT_1A receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT_1A receptor radioligand [carbonyl-¹¹C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT_1A receptor binding potential (BP) as independent variable showed a highly significant association (r = .691, p = .002). The hypothalamic 5-HT_1A BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant (p < .01, Bonferroni corrected threshold <.0056) between 5-HT_1A BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT_1A receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT_1A receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT_1A receptor distribution have been reported in affective disorders, future studies should focus on these interactions.     

Sex-specific effects of CNTF, IL6 and UCP2 polymorphisms on weight gain

The human proteins ciliary neurotrophic factor (CNTF) and interleukin-6 (IL6) and their receptors share structural homology with leptin and its receptor. In addition, uncoupling protein-2 (UCP2) has been shown to participate the regulation of leptin on food intake. All three proteins are active in the hypothalamus. Experiments have shown that CNTF and IL6, like leptin, can influence body weight in humans and animals, while the effect of UCP2 is not consistent. In a Dutch general population (n = 545) we investigated associations of CNTF (null G/A, rs1800169), IL6 (174 G/C, rs1800795) and UCP2 (A55V, rs660339 and del/ins) polymorphisms with weight gain using interaction graphs and logistic regression analysis. The average follow-up period was 6.9 years. Individuals who gained weight (n = 264) were compared with individuals who remained stable in weight (n = 281).In women the CNTF polymorphism (odds ratio (OR) = 2.15, 95%CI: 1.27-3.64, p = 0.004) and in men the IL6 polymorphism by itself (OR = 2.26, 95%CI: 1.08-4.75, p = 0.03) or in combination with the CNTF polymorphism, were associated with weight gain. Furthermore, CNTF and IL6 polymorphisms in interaction with UCP2 polymorphisms had similar strong effects on weight gain in women and men, respectively. All observed effects were statistically shown to be independent of serum leptin level. These results are incorporated in a biological model for weight regulation with upstream effects of CNTF and IL6, and downstream effects of UCP2.The results of this study suggest a novel mechanism for weight regulation that is active in both women and men, but strongly influenced by sex.